Long non-coding RNA HNF1A-AS1 promotes hepatocellular carcinoma cell proliferation by repressing NKD1 and P21 expression

Biomed Pharmacother. 2017 May:89:926-932. doi: 10.1016/j.biopha.2017.01.031. Epub 2017 Mar 8.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Recent evidences have demonstrated that long non-coding RNAs (lncRNAs) act as key regulators of tumor development and progression including HCC. In the study, we showed that the expression level of HNF1A-AS1 was up-regulated in HCC cell lines. Furthermore, CCK-8 cell proliferation assays and cell cycle analysis showed that HNF1A-AS1 over-expression facilitated HCC cell proliferation by promoting the cell proliferation and S-phase progression, whereas HNF1A-AS1 knockdown had the opposite effect. Western-blotting analysis revealed that knockdown of HNF1A-AS1 inhibited the cycle-relative protein cyclin-D1 and PCNA expression in HCC cells. Mechanism, RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays showed that by interacting with enhancer of zeste homolog 2 (EZH2), HNF1A-AS1 promoted HCC cell proliferation by repressing the NKD1 and p21 expression. These results suggested that HNF1A-AS1 may contribute to HCC progression, which may be an effective therapeutic target for patients.

Keywords: Cell proliferation; HNF1A-AS1; Hepatocellular carcinoma; NKD1; P21.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Calcium-Binding Proteins
  • Carcinoma, Hepatocellular / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Proliferation / physiology*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Hepatocyte Nuclear Factor 1-alpha / metabolism*
  • Humans
  • Liver Neoplasms / metabolism*
  • Membrane Proteins
  • Protein Binding
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Atp5md protein, rat
  • CDKN1A protein, human
  • Calcium-Binding Proteins
  • Carrier Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Membrane Proteins
  • NKD1 protein, human
  • RNA, Long Noncoding